Physical Sciences Inc. (PSI), with support from Carl Zeiss Ophthalmic Systems (CZOS), has successfully completed a Phase I research program demonstrating the feasibility of combining Optical Coherence Tomography (OCT) and patented PSI retinal tracking technology. A Phase II research and development program is proposed to create Tracking OCT (TOCT) instrumentation that will significantly enhance retinal imaging and morphometric diagnostics. The capability to reproducibly map three-dimensional structures in the living eye, approaching cellular resolution, will lead to improved understanding of disease processes and improved sensitivity and specificity of diagnostic procedures. At present, the slow speed of 2-D OCT imaging limits diagnostic potential in the clinic. Normal eye movement often renders transverse OCT scan registration difficult to correct, creating image errors and artifacts. PSI's retinal tracking technology is a highspeed, non-imaging system that uses retinal landmarks to achieve precise transverse image registration, and with tracking errors smaller than the OCT beam diameter. Precisely aligned scans can be compared months, or years apart. Frame averaging techniques can reduce OCT speckle noise without loss of transverse or longitudinal resolution. Adjacent 2-D scans can be concatenated into 3-D data sets. Standard resolution and high resolution TOCT systems will be assembled and tested in clinical studies at New England Eye Center.